The orderly transport of proteins within the secretory pathway of eucaryotic cells is mediated by the specific recognition and fusion of transport vesicles with distinct target organelle-associated membrane proteins termed SNAREs. In our attempt to identify the transport route taken by MHC class II molecules to intracellular antigen processing compartments, we have screened a human B cell cDNA library in search of genes regulating vesicular traffic in lymphocytes. We have isolated the cDNA encoding human syntaxin 5, a transmembrane protein whose rat and yeast homologs regulate endoplasmic reticulum-to-Golgi apparatus transport. We have also isolated the cDNA for SNAP-23, a ubiquitously expressed membrane-associated protein potentially involved in facilitating vesicle docking and fusion with the plasma membrane. We are also investigating the role that post-translational modification plays in the regulation of intracellular MHC class II transport. We have identified the phosphorylation sites on the MHC class II-associated invariant chain, and are working to understand the regulation of invariant chain phosphorylation in the context of MHC class II- restricted antigen processing and presentation.